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Co-regulated transcriptional networks contribute to natural genetic variation in Drosophila sleep

Nature Genetics volume 41, pages 371–375 (2009)Cite this article

Abstract

Sleep disorders are common in humans, and sleep loss increases the risk of obesity and diabetes1. Studies in Drosophila2,3 have revealed molecular pathways4,5,6,7 and neural tissues8,9,10 regulating sleep; however, genes that maintain genetic variation for sleep in natural populations are unknown. Here, we characterized sleep in 40 wild-derived Drosophila lines and observed abundant genetic variation in sleep architecture. We associated sleep with genome-wide variation in gene expression11 to identify candidate genes. We independently confirmed that molecular polymorphisms in Catsup (Catecholamines up) are associated with variation in sleep and that P-element mutations in four candidate genes affect sleep and gene expression. Transcripts associated with sleep grouped into biologically plausible genetically correlated transcriptional modules. We confirmed co-regulated gene expression using P-element mutants. Quantitative genetic analysis of natural phenotypic variation is an efficient method for revealing candidate genes and pathways.

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Figure 1: Variation in sleep phenotypes among wild-derived inbred lines.
Figure 2: Association between sleep phenotypes and Catsup polymorphisms.
Figure 3: Validation of sleep candidate genes.
Figure 4: Analyses of candidate genes associated with natural variation in sleep phenotypes.

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Acknowledgements

This work was supported by National Institutes of Health grants R01 GM 45146, R01 GM 076083 and R01 AA016560 to T.F.C.M. and the National Sleep Foundation Pickwick Fellowship to S.T.H. We thank D. Reif for assistance with Catsup permutation tests, K. Jordan for assistance with the genetic correlation data and R. Anholt for comments on the manuscript. This is a publication of the W.M. Keck Center for Behavioral Biology.

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Authors and Affiliations

  1. Department of Genetics, North Carolina State University, Raleigh, 27695, North Carolina, USA

    Susan T Harbison, Mary Anna Carbone, Julien F Ayroles, Richard F Lyman & Trudy F C Mackay

  2. W.M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, 27695, North Carolina, USA

    Susan T Harbison, Mary Anna Carbone, Julien F Ayroles, Eric A Stone, Richard F Lyman & Trudy F C Mackay

  3. Department of Statistics, North Carolina State University, Raleigh, 27695, North Carolina, USA

    Eric A Stone

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Contributions

S.T.H. and T.F.C.M. conceived of the experiment. S.T.H measured sleep phenotypes in all lines and measured expression levels in P-element insertions. M.A.C. generated whole-genome expression data and sequenced Catsup. S.T.H, J.F.A. and E.A.S. analyzed the data. R.F.L. generated the 40-line reference panel. S.T.H. and T.F.C.M wrote the paper.

Corresponding author

Correspondence to Trudy F C Mackay.

Supplementary information

Supplementary Text and Figures

Supplementary Tables 1,3,4 and 6, Supplementary Figure 1 and Supplementary Methods (PDF 940 kb)

Supplementary Table 2

SFPs and modules of correlated transcripts associated with quantitative sleep traits (XLS 541 kb)

Supplementary Table 5

GO categories (XLS 151 kb)

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Harbison, S., Carbone, M., Ayroles, J. et al. Co-regulated transcriptional networks contribute to natural genetic variation in Drosophila sleep. Nat Genet 41, 371–375 (2009). https://doi.org/10.1038/ng.330

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